AURA-LV and AURORA Trials Facts
Clinical Research on Lupkynis™ (voclosporin)
- Aurinia Pharmaceuticals first began clinical studies of Lupkynis™ (voclosporin) involving patients in 2015
- The U.S. Food and Drug Administration (FDA) granted Fast Track designation for Lupkynis in March 2016.
- The AURA–LV trial (Aurinia Urinary Protein Reduction in Active Lupus with Voclosporin) was a 48-week trial comparing the efficacy of two doses of Lupkynis added to current standard of care of mycophenolate mofetil (MMF) against standard of care with placebo in achieving a complete remission (CR) in patients with active lupus nephritis (LN). 265 patients were enrolled at centers in 20 countries worldwide. Top line results of the Phase 2b AURA-LV trial were announced March 1, 2017. (24-week results were announced on September 29, 2016.)
- The AURORA clinical trial was a 52-week phase III global, double-blind, placebo-controlled study to evaluate whether Lupkynis when added to background therapy of MMF can increase speed of and overall renal response rates in the presence of low dose steroids. 357 patients with active LN were enrolled in this study across sites in 27 countries. The first patients in the study were dosed in May 2017. Results of the AURORA study were announced on December 4, 2019.
- Renal response was defined as urinary protein-to-creatinine ratio (UCPR) of ≤ 0.5 mg/mg, eGFR ≥ 60 mL/min/1.73 m2, or no confirmed decrease from baseline in estimated glomerular filtration rate (eGFR) of > 20%, presence of sustained, low dose steroids and no administration of rescue medication.
Results of Clinical Studies of Lupkynis
- In late 2019 Aurinia reported uniformly positive results from the AURORA trial of Lupkynis – the first late-stage clinical trial of any drug in lupus nephritis to meet all primary and secondary endpoints.
- Lupkynis plus MMF plus Prednisone was superior to MMF plus Prednisone alone. Lupkynis also well-tolerated with no unexpected safety signals.
- “These two studies, along with the growing body of data supporting the use of Lupkynis, clearly demonstrate the benefits of this therapy to provide effective and safe treatment,” said Neil Solomons, M.D., Chief Medical Officer of Aurinia.
- The integrated data [presented by Dr. Ellen Ginzler at ACR 2020] demonstrated that patients with LN treated with Lupkynis in combination with MMF and low-dose steroids achieved statistically superior and a more rapid renal response (RR) compared to patients treated with MMF and steroids alone.
- Treatment with Lupkynis resulted in clinically meaningful and a statistically significant higher RR rate of 43.7% compared to 23.3% in the control arm at one year, and at six months (Lupkynis 31.7%; placebo 20.3%).
- A 50% reduction in UPCR from baseline at any time was achieved by 93.7% of patients treated with Lupkynis compared with 75.2% of patients receiving placebo.
- The time taken to reach a 50% reduction in UPCR was significantly shorter for the Lupkynis group than the placebo group.
- At one year, 160 (75.8%) patients in the Lupkynis arm and 150 (73.9%) patients in the placebo arm were on oral prednisone ≤ 2.5 mg /d.
- The odds of achieving a renal response in the Lupkynis arm were 2.76-fold greater than control, while maintaining a comparable safety profile and with minimal impact on mean eGFR at one year of treatment.
- These [pooled data] results are encouraging as the rapid reduction of proteinuria within the first year of treatment is a critical clinical response associated with preserving renal function and improving long-term outcomes for patients with lupus nephritis.
Results in Minorities and Other Subset Populations
- The presented data demonstrated clinically meaningful benefits of Lupkynis for trial participants across ethnicities and self-reported race.
- Significant renal response rates were seen for Hispanic/Latino patients in the Lupkynis arm (38.6%) versus control arm (18.6%), as well as for non-Hispanic/Latino patients in the Lupkynis arm (41.8%) versus the control arm (24.6%).
- Similar renal response rates for Lupkynis vs control arm were seen for Blacks (46.2% vs 15.8%) and Asians (41.5% vs 17.9%). Furthermore, all other pre-specified subgroup analyses (age, sex, race, biopsy class, region, and prior MMF use) favored Lupkynis.
- In a pooled analysis [of data from the AURA-LV and AURORA trials, adult patients with lupus nephritis treated with Lupkynis achieved meaningful rapid reductions in proteinuria, including patients in the Hispanic subgroup, a high-risk lupus nephritis population.
- The drug-to-drug interaction (DDI) study demonstrated for the first time that Lupkynis does not have a meaningful drug-drug interaction when administered with MMF. The DDI study was conducted to determine whether the drug concentration was within the therapeutic range and was below the toxic level.
- Lupkynis does not have clinically significant impacts on mycophenolic acid (MPA) blood concentrations, which indicates that Lupkynis and MMF can be administered concomitantly without the need to adjust the dose of MMF.
- Lupkynis was well tolerated with no unexpected safety signals. Serious adverse events (SAEs) were reported in 20.8% of Lupkynis patients vs. 21.3% in the control arm. Infection was the most commonly reported SAE with 10.1% of Lupkynis patients versus 11.2% of patients in the control arm.
- The Lupkynis arm showed no significant decrease at week 52 in estimated glomerular filtration rate (eGFR) or increase in blood pressure, lipids or glucose.
More about Lupkynis (voclosporin)
from the National Resource Center on Lupus